This program is a continuation of our studies to develop and evaluate appropriate animal models and methodology to study prostatic cancer. The Dunning series of R-3327 tumors are transplantable and have many important properties such as a slow growth rate, androgen sensitivity, and a well differentiated histology. The subcutaneous transplants of the tumors do have the ability to metastasize but with a low incidence. It is proposed to study factors affecting the metastatic rate and pattern of this important tumor. This study has included a detailed characterization of the various R-3327 tumors at a biochemical, histological and pharmacological level. New models have been developed and are proposed to cover the spectrum of different tumors that exist in human prostatic adenocarcinoma. These include: well differentiated to anaplastic; hormone (androgen) sensitive to insensitive; slow growth to moderate rates. The unique property of the Dunning R-3327 series is that it is capable of developing into these specific types of tumors in animals. The Dunning model is also unique in having a slow growth rate and also responding to castration or estrogen therapy followed by subsequent relapse to an androgen insensitive state; this is similar to what is observed in humans with prostatic cancer. Studies proposed include: cell kinetics; nucleic acid synthesis; development of new tumor lines and cell cultures; evaluation of clone selection and progression theories; evaluation of factors predicting hormone sensitivity and tumor growth rate and the evaluation of a series of cancer chemotherapeutic agents used in combination and with the adjuvant therapy.